Methods of diagnosing complicated urolithiasis and predicting urolithiasis

ABSTRACT

A method of diagnosing complicated urolithiasis consists in testing for and finding the presence of albumen in a urine sample. A portion of said sample is dried and a crystallographic study is performed. On finding a marginal amorphous area, accommodating a central crystalline area, pyelonephritis is diagnosed. On discovering a full crystalline area (i.e. with no marginal amorphous area), calculous pyelonephritis is diagnosed. The method of prognostication involves testing for and finding the absence of albumen in a urine sample. A portion of the urine sample is mixed with a 8-12% protein solution, the mixture is then dried and a crystallographic study is conducted. With a full non-transparent crystallization of the sample (i.e. without the marginal amorphous area), urolithiasis is prognosticated.

This is a continuation of copending application(s) Ser. No. 07/895,324filed on Jun. 8, 1992 now abandoned which is a continuation ofInternational Application PCT/SU91/00140 filed on Jul. 9, 1991.

FIELD OF THE INVENTION

The invention relates to medicine, more specifically, to methods ofdiagnosing complicated urolithiasis and prognosticating same.

At present for purposes of diagnosing said urolithiasis, particularlypyelonephritis, calculous pyelonephritis, use is made of clinicallaboratory examination of urea, the X ray and ultrasound analysis ofkidneys and urea excretory tracts.

A possibility of the onset of urolithiasis is evaluated if risk factorsare available such as hereditary predisposition and endemicity.

BACKGROUND ART

Known in the art is a method of diagnosing pyelonephritis based onlaboratory methods of investigations one of which is determination ofthe contained albumen in urea. The method is based on coagulation of thealbumen with chemical reagents, for example, nitric acid, sulfosalicylicacid, to mention only a few; and physical methods, particularly, heatingsaid urea etc (Spravochnik po klinicheskim laboratornym metodamissledovaniya. Edited by E. Kost, Moscow, MEDITSINA Publishers, 1975;Laboratornye metody issledovaniya v klinike. Spravochnik, edited by V.Menshikov, Moscow, MEDITSINA Publishers, 1987).

Also known is a method for the examination of a urea sample containingalbumen which is based on crystallography. This method can also be usedfor diagnosing pyelonephritis. It consists in the following: a samplefrom the top layer of settled urea is applied to a microscope slide tobe dried to complete crystallization and the presence of albumen isestablished in the urea under examination, when a marginal amorphousarea shows itself. Along with this, glucose is found in the urea if acrystallization area is absent altogether (SU, A1, 1573425).

Known in the art is a method for diagnosing ureteral calculus diseasewhich is based on finding calculus formation in cases where aprecipitate is observed in freshly excreted urine or a short while afterurination (V. Predtechensky "Rukovodstvo po klinicheskim laboratornymissledovaniya", MEDITSINA, 1964, pp.420-446). Such examinations areperformed in native urea. In order to slow down evaporation anddesiccation, a urine sample is covered with cover glass.

Also known is a method for prognosticating urolithiasis according towhich determination is given to a degree of risk of calcium phosphatecrystallization in urine by counting the formed crystals of specificsize according to mathematical calculations with account taken ofcertain factors ("Urological Research", N 2, 15, 1987, Springer-Verlag,H.-G. Tiselius "Measurement of the Risk of Calcium PhosphateCrystallization in Urine", s.79-81).

Also known is a method for prognosticating urolithiasis which allows fora combined calculation of the morphological parameters of a cuppelvicsystem with the clinical-chemical parameters of urine on the basis of adiscriminant analysis with consideration of eight functions for 3-10parameters ("European Urology", 16, N 3, 1989, S. Karger A. G. Basel; E.Schultz, R. Boerner, P. Brundig, F. Maeurer "Influence of DifferentFactors on the Formation of Calcium Oxalate Stones", s.218-222).

DISCLOSURE OF THE INVENTION

It is the principal object of the present invention to specify thediagnosis of complicated urolithiasis, more specifically, calculouspyelonephritis, and also predict said urolithiasis in healthy persons onexamination when urine examination has no deviations from normal andsubjective complaints are absent.

This object is accomplished by the claimed new method of diagnosingcalculous pyelonephritis. In addition to clinical examination of a urinesample for the presence of albumen, a portion of the urine sample isadditionally taken to be applied to the surface of glass, and dried,followed by crystallographic examination. The presence in the driedportion of said sample of a marginal amorphous area, within which thecentral crystalline area is located, points to the presence ofpyelonephritis. If said amorphous area is absent, i.e. inspectionreveals a full crystalline area, the diagnosis is calculouspyelonephritis.

The claimed invention makes it possible to obtain a simple method ofdiagnostics in clinical laboratory practice requiring no X ray orultrasound examination, a factor that enables one to avoid radiation andultrasound loading on the patient and also the use of expensiveapparatus which is not readily available. The method can well be carriedout by a person of skill in the art.

The object of the invention is accomplished by the claimed method forpredicting urolithiasis in healthy persons. In addition to the clinicalexamination of urine samples for absence of albumen, to said urinesample portion is additionally added 8-12% of a protein substance, forexample, albumen. A mixture sample is applied to a glass substrate to bedried at room temperature for about a day and crystallographicinvestigations are performed. If the dried mixture shows a fullnon-transparent crystallization, i.e. there is observed the absence ofthe protein amorphous area in the urine/protein mixture, theprognostication is urolithiasis.

Performance of timely diet measurements and medicament therapy with suchpatients can prevent stone formation. The claimed method contributes toprognosticating urilithiasis in persons having not only hereditarypredisposition but also any forms of acquired urolithiasis, i.e.actually 100% of cases.

The method of patent protection sought assures the following advantages:to predict urolithiasis rapidly, without a patient's pre-preparation andwithout using special equipment and expensive reagents.

The method can be introduced into practice on a wide scale in allmedical establishments and provides a possibility of mass-scaleexaminations during preventive treatment directed to prevention of theprogress of ureteral calculus disease.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is explained by a clear description of its dependentfeatures with reference to the accompanying drawings in which:

FIG. 1 shows a marginal amorphous area accommodating a centralcrystalline area with a positive albumen sample in urine. Conclusion:pyelonephritis of non-calculous origin.

FIG. 2 shows a full crystalline area, in other words, no marginalamorphous area is present, which indicates, in case of a positivealbumen sample in urine, pyelonephritis of calculous origin.

FIG. 3 shows a marginal amorphous area accommodating a centralcrystalline area, in the sample of a mixture of urine and albumensolution, the albumen sample in urine is negative. Conclusion: nodiagnosis of urolithiasis.

FIG. 4 shows a full crystalline area--the absence of a marginalamorphous area in the sample of a mixture of urine and albumensolution--with a negative albumen sample in urine. Conclusion:urolithiasis is prognosticated.

BEST MODE OF CARRYING OUT THE INVENTION

The claimed method of diagnosing complicated urolithiasis, particularlypyelonephritis, and calculous pyelonephritis is carried out in thefollowing manner.

Urine is sampled and subjected to clinical laboratory examination forthe presence of albumen therein. In case of albumen being found in theurine, another portion of the urine sample/0,01-0,02/ is applied to thesurface of a microscope slide and allowed to stay at room temperature tocomplete dryness (30-40 minutes). The dried urine sample is subjected tovisual crystallographic study, followed by the performance of acomparative analysis of crystallization of the urine sample and aqualitative reaction for albumen for example, in a test tube.

EXAMPLE 1

Patient A. On crystallographic examination two areas are discoveredvisually: in the center--an area of crystalline salts, on the margin--anamorphous area. A positive qualitative reaction for albumen is found.

Conclusion: pyelonephritis of non-calculous origin.

Clinical diagnosis: chronic pyelonephritis (see FIG. 1).

EXAMPLE 2

Patient V. On crystallographic examination one area is found visuallywhich is completely covered with salt crystals. A positive qualitativereaction for albumen is found.

Conclusion: calculous pyelonephritis (see FIG. 2).

Clinical diagnosis: calculus. Secondary pyelonephritis.

The claimed method was used for verifying the presence of albumen in 61samples in a range of concentrations of from 0,033 g/l to 0,495 g/l.

The claimed method makes it possible to perform a differential diagnosisof pyelonephritis and calculous pyelonephritis and is substantiated bythe fact that in some pyelonephritis cases, etiology may be "calculous".This method works in 100% of cases and must be carried out at the veryfirst stages of patients' inspection.

The method of diagnostics was verified on 36 patients. Results are givenin Table 1.

The claimed method for the prognostication of urolithiasis is carriedout as follows:

An arbitrarily excreted urine portion is taken in a healthy person andsubjected to a clinical laboratory examination for the absence ofalbumen. Furthermore, from the top layer of a settled urine portion afraction thereof is collected and mixed with a 8-12% albumen-containingsolution. Said mixture having a volume of 20-50 ml is then applied to aglass substrate and allowed to stay at room temperature for a day.

                                      TABLE I                                     __________________________________________________________________________    Data on patients' clinical-laboratory examination                             Test for calculous pyelonephritis                                             dried urine   presence of                                                                            Discovery of concrements in examin.                    No.                                                                              sample, type                                                                             albumin in urine                                                                       X ray     Ultrasound                                                                            Clinical diagnosis                   1  2          3        4         5       6                                    __________________________________________________________________________    1. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       2. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       3. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       4. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       5. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       6. full       +        yes       yes     calculous                               crystallization     /X-ray-negative/  pyelonephritis                       7. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       8. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       9. full       +        yes       yes     calculous                               crystallization                       pyelonephritis                       10.                                                                              full       +        no        yes     calculous                               crystallization     /X-ray-negative/  pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        no        yes     calculous                               crystallization     /X-ray-negative/  pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               full       +        no        yes     calculous                               crystallization     /X-ray-negative/  pyelonephritis                       20.                                                                              full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          full       +        yes       yes     calculous                               crystallization                       pyelonephritis                          presence of marginal                                                                     +        no        no      chronic                                 amorphous area                        pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                     30.                                                                              presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                        presence of marginal                                                                     +        no        no      chronic                                 amorphous area and                    pyelonephritis                          crystalline one in the                                                        conter                                                                     __________________________________________________________________________

By way of control, a portion of urine is applied parallel with a sample,without adding an albumen substance. The thus dried mixture of saidurine and albumen solution are subjected to visual crystallographicexamination.

In conclusion, a correlation is made of the observable patterns ofcrystallization of a urine mixture sample for the presence of centraland marginal areas.

EXAMPLE 3

Patient S. On crystallographic examination of a mixture of urine andalbumen solution, there are visually found two areas: in the center--acrystallization area, on the margin--a transparent amorphous area. Anegative qualitative reaction for albumen is found.

Conclusion: no prognostication of urolithiasis.

Clinical diagnosis: right kidney prolapse (see FIG. 3).

EXAMPLE 4

Patient D. On crystallographic examination of a mixture of urine andalbumen solution there is visually discovered one area that iscompletely crystallized.

Conclusion: urolithiasis is predicted.

Clinical diagnosis: nephritis (see FIG. 4).

It is worthy to note that in the two-above-described Examples 3 and 4,the control samples provided one and the same picture, namely, onecompletely crystallized area, i.e. no result has been yielded as regardsprediction of the disease.

The claimed method enables one to prognosticate urolithiasis in healthypersons and to take measures towards preventing stone formation. Themethod is simple, and easy to implement.

The method was checked on 1088 practically healthy people. Results aregiven in Tables 2 and 3.

                                      TABLE 2                                     __________________________________________________________________________    Results of examination of practically healthy persons                                                                  Concrements found in USI 22                             Concrements found in                                                                     Concrements found in                                                                     months after observation of:                            USI* of 84 persons                                                                       USI of 24 persons in                                                                     84 persons with                                                                       15 persons with              Number of people   in whom no urolithias                                                                    whom urolithiasis was                                                                    no urolithiasis                                                                       urolithiasis                 Total                                                                              no prognosis                                                                          prognosis                                                                           was prognosticated                                                                       prognosticated                                                                           prognosis                                                                             prognosis                    Number                                                                             urolithiasis                                                                          urolithiasis                                                                        yes  no    yes  no    yes no  yes no                       __________________________________________________________________________    108  84      24    0    84    9    15    0   84  7   8                        100% 77.8%   22.2%       100% 37.5%                                                                              62.5%      100%                                                                             46.7%                                                                             53.3%                    __________________________________________________________________________     *ultrasound inspection                                                   

                                      TABLE 3                                     __________________________________________________________________________    Results of examination of 15 persons with the prognosis                       of urolithiasis according to the claimed method                               Presence /+/ or absence(-) of concrements in kidneys,                         urine tracts on the basis of USI                                                 at the moment                                                              N  of prognostication                                                                     6-8 month after                                                                       12-14 months after                                                                      18 months after                                                                       22 months after                         __________________________________________________________________________    1. -        +        +*       +       +                                       2. -        +       +         +       +                                       3. -        -       +         +        +*                                     4. -        -       +         +       +                                       5. -        -       -         +       +                                       6. -        -       -         -       +                                       7. -        -       -         not performed                                                                          +*                                     8. -        -       -         -       -                                       9. -        -       -         -       -                                       10.                                                                              -        -       -         -       -                                          -        -       -         -       -                                          -        -       -         -       -                                          -        -       -         -       -                                          -        -       -         -       -                                          -        -       -         -       -                                       __________________________________________________________________________     *a fit of kidney colic was recorded.                                     

Industrial applicability

The invention may find a variety of applications in the practice of allmedical establishments as not requiring expensive facilities andreagents. Its advisable to put this invention into practice duringmass-scale prophylactic examinations of population for purposes ofcarrying out preventive treatment directed to prevention of the progressof urolithiasis.

We claim:
 1. A method for diagnosing pyelonephritis of a non-calculousorigin by examination of a urine sample comprising separating the urinesample into at least two portions, testing a first of said two portionsfor presence of albumen,drying a second of said portions so that itcrystallizes, and examining for the presence of a marginal amorphousarea in the dried crystallized second portion.
 2. A method fordiagnosing calculous pyelonephritis by examination of a urine samplecomprising separating the urine sample into at least two portions,testing a first of said at least two portions for presence of albumen,drying a second of said portions so that it crystallizes and examiningfor absence of a marginal amorphous area in the dried crystallizedsecond portion.
 3. A method for predicting urolithiasis by examinationof a urine sample comprising separating the urine sample into at leasttwo portions, screening a first of said portions for the absence ofalbumen, mixing the second portion with an 8-12% albumen solution,drying the resultant mixture at room temperature for about a day andscreening to detect whether there is substantially completecrystallization.